3,5-di-tert-butylsalicylaldehyde, I, is a starting material for the preparation of a preferred manganese salen catalyst of formula II [see Jacobsen et al., J. Am. Chem. Soc. 113, 7063-7064 (1991)] ##STR1##
3,5-Di-tert-butylsalicylaldehyde was prepared by Jacobsen et al. by the reaction of 2,4-di-tert-butylphenol with formaldehyde in the presence of SnCl.sub.4 and 2,6-lutidine (Casiraghi et al., J.C.S.P.1, 1980, 1862-1865). The use of relatively expensive reagents such as SnCl.sub.4 and lutidine, and the production of hazardous wastes make the procedure of Casiraghi unattractive for large-scale synthesis.
It is known that phenols and other activated aromatic compounds can be converted to the corresponding aldehydes by treatment with hexamethylenetetramine (HMT) (formula III). ##STR2## The reaction is known in the art as the Duff reaction; it has been reviewed by Blazevic et al. [Synthesis, 1979, 164-167]. The Duff reaction is commonly carried out with HBO.sub.2 in dry glycerol, although variations have been reported with trifluoroacetic acid and glacial acetic acid. Unfortunately, although the Duff reaction is usually successful with other activated phenols, it is notoriously poor when the substrate is a 2,4-dialkylphenol. For example, Blazevic et al. (op. cit.) report the formulation of 2-methyl-4-neopentylphenol using glycerol/boric acid in 19% overall yield. When Komissarova et al. attempted formulation of 2,4-di-tert-butylphenol using hexamethylenetetramine in the Duff reaction, they observed that the only product was a dihydro-1,3-benzoxazine [Chemical Abstracts, 110: 212723c]. ##STR3##
Yahagi reported that the corresponding 1,3-benzoxazine could be prepared very efficiently from 2,4-dimethylphenol and hexamethylenetetramine [Chemical Abstracts, 93: 8106e].
Because persons of skill in the art believed that the Duff reaction with HMT and acid was not preparatively useful for dialkyl salicylaldehydes, Zigeuner and Jellinek [Monatsh. Chem. 90, 297-305 (1959) p. 299] proposed a different synthetic route. They stated that "On the basis of the oxidative cleavage of the dibenzylamines . . . which proceeds in high yield, a new synthesis of 2-hydroxy-3,5-disubstituted benzaldehydes, which are difficult to prepare by the usual preparative methods, was developed." Their method comprised preparing a dibenzylamine from the reaction of an appropriate phenol with hexamethylenetetramine followed by oxidation of the resulting dibenzylamine to the benzaldehyde using sodium m-nitrobenzenesulfonate in aqueous acetic acid. ##STR4## No examples of the direct conversion of 2,4-dialkylphenols to 3,5-dialkylsalicylaldehydes in good yields using hexamethylenetetramine are found in the literature.
It has now been surprisingly found that under a specific set of conditions it is possible to prepare 3,5-di-tert-butylsalicylaldehyde from 2,4-di-tert-butylphenol and hexamethylenetetramine in yields that are feasible for large scale production.